Nanobodies Keep the Immune System Alert to Cancer Cells, Reducing Tumor Growth
New research has shown that nanobody treatments that block PD-L1 can reduce tumor growth by about 50%.
For nearly a decade, JABSOM researcher Stefan Moisyadi, PhD, has been chasing an idea he believes could change how we fight cancer. What he found could be a game-changer: a tiny molecule called a nanobody that may succeed where today’s immunotherapy drugs often fail.
“Antibodies won the Nobel Prize for immunotherapy,” Moisyadi said. “They work in some cancers, but not all. In colorectal cancer, they hardly work at all. But when we used nanobodies, bingo, it worked.”
The recently published research in eGastroenterology explains how Moisyadi and his colleagues at JABSOM, UH Cancer Center and UH’s College of Tropical Agriculture and Human Resources have discovered a way to use mRNA to make the body produce tiny proteins called nanobodies that block a molecule known as PD-L1. This is a major breakthrough because tumors often use PD-L1 to hide from the immune system. Normally, immune cells called T-cells, can recognize cancer cells as foreign and attack them, but when a tumor produces PD-L1, it effectively “turns off” those T-cells, stopping them from doing their job.
By using nanobodies to block PD-L1, the immune system stays alert, recognizes the cancer cells, and attacks them, giving the body a better chance to fight the tumor.
Moisyadi’s team discovered that these nanobodies, unlike conventional monoclonal antibodies, are one-tenth the size, cheaper to produce, and tougher under stress.
“They don’t trigger an immune response in the patient,” Moisyadi explains. “They penetrate better because they’re small. They can even refold back to their original shape when the condition they find themselves in changes for the better. Basically, they’re indestructible — they work much better and they’re cheaper.”
Moisyadi says, unlike traditional antibody treatments, which can cost cancer patients more than $200,000 a year, nanobody therapy, delivered as a type of mRNA similar to the COVID-19 vaccines, could dramatically reduce that cost.
“People can’t afford antibody treatments,” Moisyadi said. “Here we make an RNA version. The patient’s own cells turn it into a protein, without touching the genome. It goes into the circulation, finds the tumor, and blocks PD-L1. It’s thousands of dollars, not hundreds of thousands.”
In mouse models of colorectal cancer, the nanobody treatment reduced tumor growth by about 50%, a striking result in a cancer that doesn’t typically respond to immunotherapy.
“They work in every cancer. They will work in everything,” Moisyadi said. “We've shown that both with DNA and mRNA, the monoclonal antibodies don’t work well with PD-L1 in colon cancer. In our case, nanobodies knock the colon cancer right down.”
The science is promising, and Moisyadi doesn’t want the state or local researchers to let this breakthrough slip away.
“Hawaiʻi could become the nanobody therapy state of the world,” he said. “We need to have leaders' buy-in because everyone here is still focused on antibodies.”
Moisyadi is now collaborating with the University of Maryland, Baltimore County to explore nanobody therapies for aggressive brain tumors, but he wishes more of the work could stay in Hawaiʻi, where the discovery began.
“This works,” he said. “It works in cancer. It works in other projects. We have the chance to be on the cutting edge. But we need leadership to see it and move it forward.”
Reference: Chu WM, Ma L, Hew B, et al. Immunotherapy against colorectal cancer via delivery of anti-PD-L1 nanobody mRNA. egastro. 2025;3(3). doi: 10.1136/egastro-2024-100106
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